The program in Radiobiology & Radiotherapy (RR) comprises a broadly based, multifaceted research effort in radiation therapy, radiation biology, radiological physics and related areas of tumor biology. This program has been an approved component of the Yale Cancer Center Grant for over 25 years. Its long-term goal is to improve the treatment of cancer in general and in particular, the effectiveness of radiation therapy. The program includes a broad spectrum of activity that extends from laboratory-based experimental research to clinical investigation, and features investigators associated with 16 departments. Some of the key themes include studies of carcinogenesis, genetic instability and cell growth control; elucidation of DNA repair pathways; investigation of tumor hypoxia and development of hypoxia-targeted cancer therapies; molecular correlations with outcomes in radiation therapy; and improvements in radiation dosimetry, imaging, and delivery. The majority of RR members have rich interactions with the Yale Cancer Center (YCC) membership, stimulating translational research that is in turn facilitated by other YCC Research Programs and by extensive use of Shared Resources. The numerous cancer-related grand rounds, seminars, meetings, and journal clubs sponsored by the YCC, along with the weekly Radiobiology Workshop and Journal Club and the weekly Therapeutic Radiology Grand Rounds sponsored by the program, encourage the cooperation, mutual support, and cross stimulation among the component research teams, which leads to a more rapid and efficient application of the results of the research to clinical practice. Dr. Peter Glazer took over as program leader in 2002, replacing Dr. James J. Fischer, who had served as program leader since its inception. In the past funding period, the program expanded to include a total of 39 members affiliated with 15 departments and 3 schools, has played a role in recruiting 3 basic scientists and 6 physician investigators, and has completed renovation of 15,500 net square feet of laboratory space, partially funded by a $2M construction grant from the NIH. Dr. Glazer also serves as PI of a T32 postdoctoral training grant in Radiation Therapy, Biology and Physics, which includes a number of YCC members both within and outside of the program. In the past funding period, there have been 509 cancer related publications by members of the program, including 94 intra- and 121 inter-programmatic collaborations. Overall, the 39 investigators associated with the program have peer-reviewed funding bf $5.8M in annual total costs ($3.7M direct costs), including 17 R01s and an NIH Director's New Innovator Award. Of this funding, $2.3M annual total costs ($1.5M direct costs) comes from the NCI, including 8 ROIs, plus a T32 training grant.